White matter hyperintensities and hypobaric exposure.

OBJECTIVE: Demonstrate that occupational exposure to nonhypoxic hypobaria is associated with subcortical white matter hyperintensities (WMHs) on fluid-attenuated inversion recovery magnetic resonance imaging (MRI). METHODS: Eighty-three altitude chamber personnel (PHY), 105 U-2 pilots (U2P), and 148 age- controlled and health-matched doctorate degree controls (DOC) underwent high-resolution MRI. Subcortical WMH burden was quantified as count and volume of subcortical WMH lesions after transformation of images to the Talairach atlas-based stereotactic frame. RESULTS: Subcortical WMHs were more prevalent in PHY (volume p = 0.011/count p = 0.019) and U2P (volume p < 0.001/count p < 0.001) when compared to DOC, whereas PHY were not significantly different than U2P. INTERPRETATION: This study provides strong evidence that nonhypoxic hypobaric exposure may induce subcortical WMHs in a young, healthy population lacking other risk factors for WMHs and adds this occupational exposure to other environmentally related potential causes of WMHs. Ann Neurol 2014;76:719-726.

Headache direction and aura predict migraine responsiveness to rimabotulinumtoxin B.

OBJECTIVE: To report a retrospective analysis of patients with migraine headaches treated with rimabotulinumtoxin B as preventive treatment, investigating an association between clinical responsiveness with migraine directionality and migrainous aura. BACKGROUND: The Phase III Research Evaluating Migraine Prophylaxis Therapy studies demonstrated onabotulinumtoxin A is effective in the preventive management of chronic migraine headaches. Jakubowski et al reported greater response to onabotulinumtoxin A in migraine patients reporting inward-directed head pain (imploding or ocular) compared with outward-directed head pain (exploding), suggesting subpopulations of patients may be better candidates for its use. No correlation was found between those reporting migrainous aura and onabotulinumtoxin A responsiveness. METHODS: One hundred twenty-eight migraine patients were identified who had received rimabotulinumtoxin B injections over an average of 22 months, or 7 injection cycles. Migraine directionality was reported as inward directed (imploding, n = 72), eye centered (ocular, n = 28), outward directed (exploding, n = 16), and mixed (n = 12). RESULTS: One hundred two out of one hundred twenty-eight patients (80%) improved; of these, 58 (57%) demonstrated a >75% reduction in monthly headache frequency (">75%-responders"), 76% of which noted sustained benefits >12 months with repeated injections every 10-12 weeks. Those reporting ocular- and imploding-directed headaches were significantly more likely to be >75%-responders, compared with exploding- and mixed-directed headaches (P < .0025). Patients with ocular-directed headaches were most likely to be sustained >75%-responders. Patients reporting migrainous aura were more likely to be >75%-responders (P = .0007). Those reporting exploding- and mixed-directed headaches were more likely to be nonresponders (P < .0001). CONCLUSIONS: Reported migraine directionality and presence of migrainous aura predict migraine headache responsiveness to rimabotulinumtoxin B injections.

White Matter Integrity in High-Altitude Pilots Exposed to Hypobaria.

INTRODUCTION: Nonhypoxic hypobaric (low atmospheric pressure) occupational exposure, such as experienced by U.S. Air Force U-2 pilots and safety personnel operating inside altitude chambers, is associated with increased subcortical white matter hyperintensity (WMH) burden. The pathophysiological mechanisms underlying this discrete WMH change remain unknown. The objectives of this study were to demonstrate that occupational exposure to nonhypoxic hypobaria is associated with altered white matter integrity as quantified by fractional anisotropy (FA) measured using diffusion tensor imaging and relate these findings to WMH burden and neurocognitive ability. METHODS: There were 102 U-2 pilots and 114 age- and gender-controlled, health-matched controls who underwent magnetic resonance imaging. All pilots performed neurocognitive assessment. Whole-brain and tract-wise average FA values were compared between pilots and controls, followed by comparison within pilots separated into high and low WMH burden groups. Neurocognitive measurements were used to help interpret group difference in FA values. RESULTS: Pilots had significantly lower average FA values than controls (0.489/0.500, respectively). Regionally, pilots had higher FA values in the fronto-occipital tract where FA values positively correlated with visual-spatial performance scores (0.603/0.586, respectively). There was a trend for high burden pilots to have lower FA values than low burden pilots. DISCUSSION: Nonhypoxic hypobaric exposure is associated with significantly lower average FA in young, healthy U-2 pilots. This suggests that recurrent hypobaric exposure causes diffuse axonal injury in addition to focal white matter changes.McGuire SA, Boone GRE, Sherman PM, Tate DF, Wood JD, Patel B, Eskandar G, Wijtenburg SA, Rowland LM, Clarke GD, Grogan PM, Sladky JH, Kochunov PV. White matter integrity in high-altitude pilots exposed to hypobaria. Aerosp Med Hum Perform. 2016; 87(12):983-988.

Toxic neuropathies.

Many substances, organic and manufactured, may induce peripheral nerve damage when exposed to them. The expected clinical phenotype is of a distal, sensory or sensorimotor polyneuropathy, often painful, with axonal characteristics on electrodiagnostic and histopathologic analysis. Treatment is limited; often, the only effective management is supportive care and avoidance from or removal of the offending toxin. Fortunately, the majority of toxic neuropathies are self-limited and improves gradually after toxin elimination.

OnabotulinumtoxinA successfully used as migraine prophylaxis during pregnancy: a case report.

Botulinum toxin (btx) received U.S. Food and Drug Administration approval for migraine treatment in 2010 with a pregnancy category C. There are minimal reports of its usage in pregnancy with no adverse effects; however, there are no reported cases of usage in a known pregnancy for the successful treatment of migraines. We present a patient with a history of 4 to 5 migraines per week refractory to treatment who was subsequently controlled with btx. She initially stopped injections, however, her migraines increased to 5 to 6 per week while using standard medications for migraine treatment in pregnancy. She requested btx while 18 weeks pregnant after which she had full resolution of her migraines. She gave birth to a healthy full-term girl with no neuromuscular or developmental concerns spanning the first 6.5 years of her life, the longest reported follow-up of an infant whose mother received btx while pregnant. This is the first reported case in the literature of a patient requesting btx injections for migraine treatment while knowingly pregnant. The foundation of a btx pregnancy registry, similar to those used for antiepileptics, would be greatly beneficial to gather more safety data in regard to its further usage during pregnancy.

Inflammatory Myopathies.

Therapies that suppress or modify the immune system remain the primary treatment for the idiopathic inflammatory myopathies. Dermatomyositis (DM) and polymyositis (PM) are the two conditions that respond best to immunotherapy. Although there are no randomized controlled trials, corticosteroids, specifically high-dose oral prednisone, remain the cornerstone of management. Recent controlled clinical trials show that intravenous immunoglobulin (IVIg) is an efficacious treatment in DM. Expert clinicians are generally using this as a second-line agent or as an adjunct to prednisone. IVIg has a relatively benign side effect profile compared with chronic steroid use, but the cost of treatment, the need for repetitive treatment cycles, and the potential for serious adverse effects have kept it from being a first-line agent in DM. There have been no trials performed using IVIg in PM. Chronic immunosuppressant medications, including azathioprine, cyclosporine, and methotrexate, are also available for long-term management in patients with recalcitrant disease or side effects from extended corticosteroid use. These agents lack the troubling side effects of prednisone and are less costly than IVIg, but require close medical monitoring for adverse reactions to blood, kidney, lung, or liver. Newer medications with potentially more benign side effect profiles, such as mycophenolate mofetil and etanercept, are currently being studied, but knowledge of how effective they are and how quickly they work are not yet available. Inclusion body myositis has proven resistant to immunosuppressive medications. The response has been so consistently poor and so easily contrasted with DM that the authors wonder why these conditions are so routinely lumped together in chapters and review articles. Clearly, this is based solely on the common pathologic feature of inflammation, rather than a clear understanding of how these conditions occur, or why they do or do not respond to treatment.